Proximate and Phytochemical Investigations Probing Antioxidant and Antiepileptic Potential of Terminalia bellirica Roxb. Leaf Extracts: An In Silico Validation Study

ABSTRACT Terminalia bellirica Roxb. is a well‐known medicinal plant with diverse therapeutic uses. This study investigated the phytochemical profile of T. bellirica leaf extracts, their antiepileptic activity in an acute pentylenetetrazole (PTZ)‐induced seizure model, and the in silico validation of GC–MS–identified metabolites. Proximate analysis confirmed the presence of abundant phenolics, flavonoids, and other secondary metabolites across solvent fractions. Among the five tested extracts, the methanolic extract demonstrated the strongest free radical scavenging activity ( p < 0.01) with marked reduction in superoxide dismutase (SOD), GSH, and malondialdehyde (MDA) levels ( p < 0.0001). Likewise, in an acute epilepsy model, among others, methanolic extract significantly delayed seizure onset and reduced seizure duration ( p < 0.01)—a response comparable to diazepam. GC–MS profiling of the methanolic extract identified 12 bioactive compounds, of which three—3,4‐methylenedioxy‐ N ‐propylaminocathinone, 9,12‐octadecadienoic acid, and pentadecadienoic acid methyl ester—exhibited the highest binding affinity for the GABAA_AA receptor during molecular docking. MM‐GBSA analysis further supported the favorable binding free energies of these ligand–receptor complexes, whereas 100‐ns MD simulations (root mean square deviation [RMSD], root mean square fluctuation [RMSF], and interaction profiling) confirmed their dynamic stability and adaptability. Collectively, the experimental and computational findings highlight the antiepileptic potential of T. bellirica leaves and identify key metabolites that may contribute to GABAergic modulation.